Generic placeholder image

Current Pharmaceutical Analysis

Author(s): Wenjun Zhou, Hongqun Qiao*, Lingling Xu, Yanjuan Yuan and Qing Shao

DOI: 10.2174/1573412917999201211204108

DownloadDownload PDF Flyer Cite As
A Quantitative LC-MS/MS Method for the Simultaneous Determination of the Presence of R-α-lipoic Acid and S-α-lipoic Acid After Protein Precipitation in Rat Plasma and its Application in a Toxicokinetic Study

Page: [101 - 110] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: Lipoic acid is the only known chiral antioxidant that is both lipidsoluble and water-soluble. It is often used as a treatment for peripheral polyneuropathy caused by diabetes, alcohol, and chemicals. However, only a few long-term toxicological studies have been conducted on R-α-lipoic acid, which is a bioactive ingredient in lipoic acid.

Objective: In this study, a simple, efficient, sensitive and stable LC-MS/MS method was used to determine RLA in rats, using deu-lipoic acid as an internal standard.

Methods: The samples to be detected were plasma samples treated with protein precipitation and the simultaneous determination of the presence of R-α-lipoic acid and S-α-lipoic acid was conducted using LC-MS/MS. An isocratic elution program with a mobile phase composed of acetonitrile and 0.1% formic acid water solution (52/48) used for chromatographic separation was set up using a CHIRALPAK® IE C18 (250 mm × 4.6 mm, 5 μm) column with a flow rate of 0.9 mL/min. A negative electrospray ionization source was chosen, and the multiple monitoring (MRM) mode was applied.

Results: R-α-lipoic acid and S-α-lipoic acid both were found to be present at a linear range of 5- 5000 ng/mL. The plasma samples were stable under various storage conditions and temperatures. The toxicokinetics study indicated that there were gender differences and that R-α-lipoic acid showed bioaccumulative toxicity after long-term daily administration. In addition, R-α-lipoic acid and S-α-lipoic acid were not converted into each other in the rats.

Conclusion: The method established was successfully used for the long-term toxicokinetic study of R-α-lipoic acid administered to rats through caudal vein injection. The toxicokinetics results indicated the presence of gender differences and the toxic accumulation of R-α-lipoic acid. The two enantiomers were not converted into each other in the rats.

Keywords: R-α-lipoic acid, toxicokinetics, LC-MS/MS, isocratic elution, protein precipitation, sprague-dawley rats, intravenous injection.

Graphical Abstract

[1]
Zuliani, C.; Baroni, L. Antioxidants for the Prevention and Treatment of Multiple Sclerosis: An Overview.Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease; Watson, R.R; Preedy, V.R., Ed.; Academic Press: San Diego, 2015, pp. 341-353.
[http://dx.doi.org/10.1016/B978-0-12-411462-3.00035-7]
[2]
Andrea Moura, F.; Queiroz de Andrade, K.; Celia Farias dos Santos, J.; Oliveira Fonseca Goulart, M. Lipoic acid: its antioxidant and anti-inflammatory role and clinical applications. Curr. Top. Med. Chem., 2015, 15(5), 458-483.
[3]
Mohamed, A.; Ahmed, E.E.; Mohammed, Z.R.; Ali, E.A. An Overview of the Antioxidant Effects of Ascorbic Acid and Alpha Lipoic Acid (in Liposomal Forms) as Adjuvant in Cancer Treatment. Antioxidants (Basel, Switzerland);; , 2020, 9, . (5)
[4]
Saliq, A.M.; Krishnaswami, V.; Janakiraman, K. Kandasamy, R α-Lipoic acid nanocapsules fortified cow milk application as a dietary supplement product for anemia. Appl. Nanosci., 2020.
[5]
Liu, J.; Shen, W.; Zhao, B.; Wang, Y.; Wertz, K.; Weber, P.; Zhang, P. Targeting mitochondrial biogenesis for preventing and treating insulin resistance in diabetes and obesity: Hope from natural mitochondrial nutrients. Adv. Drug Deliv. Rev., 2009, 61(14), 1343-1352.
[http://dx.doi.org/10.1016/j.addr.2009.06.007] [PMID: 19716392]
[6]
Jalili-Baleh, L.; Forootanfar, H.; Küçükkılınç, T.T.; Nadri, H.; Abdolahi, Z.; Ameri, A.; Jafari, M.; Ayazgok, B.; Baeeri, M.; Rahimifard, M.; Abbas Bukhari, S.N.; Abdollahi, M.; Ganjali, M.R.; Emami, S.; Khoobi, M.; Foroumadi, A. Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer’s disease based on coumarin and lipoic acid scaffolds. Eur. J. Med. Chem., 2018, 152, 600-614.
[http://dx.doi.org/10.1016/j.ejmech.2018.04.058] [PMID: 29763808]
[7]
Campos, P.M.B.G.M.; de Camargo Júnior, F.B.; de Andrade, J.P.; Gaspar, L.R. Efficacy of cosmetic formulations containing dispersion of liposome with magnesium ascorbyl phosphate, alpha-lipoic acid and kinetin. Photochem. Photobiol., 2012, 88(3), 748-752.
[http://dx.doi.org/10.1111/j.1751-1097.2012.01086.x] [PMID: 22236139]
[8]
Zhou, W-J.; Ni, Y.; Zheng, G-W.; Chen, H-H.; Zhu, Z-R.; Xu, J-H. Enzymatic resolution of a chiral chlorohydrin precursor for (R)-α-lipoic acid synthesis via lipase catalyzed enantioselective transacylation with vinyl acetate. J. Mol. Catal., B Enzym., 2014, 99.
[http://dx.doi.org/10.1016/j.molcatb.2013.11.005]
[9]
Gunsalus, I.C.; Barton, L.S.; Gruber, W. Biosynthesis and Structure of Lipoic Acid Derivatives1. J. Am. Chem. Soc., 1956, 78(8), 1763-1766.
[http://dx.doi.org/10.1021/ja01589a079]
[10]
Su, Q.; Liu, J-J.; Cui, W.; Shi, X-L.; Guo, J.; Li, H-B.; Huo, C.J.; Miao, Y.W.; Zhang, M.; Yang, Q.; Kang, Y.M. Alpha lipoic acid supplementation attenuates reactive oxygen species in hypothalamic paraventricular nucleus and sympathoexcitation in high salt-induced hypertension. Toxicol. Lett., 2016, 241, 152-158.
[http://dx.doi.org/10.1016/j.toxlet.2015.10.019] [PMID: 26518973]
[11]
Rochette, L.; Ghibu, S.; Richard, C.; Zeller, M.; Cottin, Y.; Vergely, C. Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Mol. Nutr. Food Res., 2013, 57(1), 114-125.
[http://dx.doi.org/10.1002/mnfr.201200608] [PMID: 23293044]
[12]
Lobato RdO. The effect of diet enriched with lipoic acid in the accumulation and metabolization of metals in different organs of Litopenaeus vannamei. Aquacult. Res., 2018, 49(12), 3702-3710.
[http://dx.doi.org/10.1111/are.13838]
[13]
Liao, C.; Dai, X.; Chen, Y.; Liu, J.; Yao, Y.; Zhang, S. Biogenic (R)-(+)-Lipoic Acid Only Constructed Cross-Linked Vesicles with Synergistic Anticancer Potency. Adv. Funct. Mater., 2019, 29(3)1806567
[http://dx.doi.org/10.1002/adfm.201806567]
[14]
A CD, R SA, J FS, L YK, Lester P. The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjects. Alternative medicine review : a journal of clinical therapeutic, 2007, 12(4).
[15]
G LE, V HL. Therapy and outcome of suspected alpha lipoic acid toxicity in two dogs. Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001), 2009, 19(5).
[16]
Hermann, R.; Niebch, G.; Borbe, H.O.; Fieger-Büschges, H.; Ruus, P.; Nowak, H. Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers. Eur. J. Pharm. Sci., 1996, 4(3), 167-174.
[http://dx.doi.org/10.1016/0928-0987(95)00045-3]
[17]
Uchida, R.; Okamoto, H.; Ikuta, N.; Terao, K.; Hirota, T. Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats. Int. J. Mol. Sci., 2015, 16(9), 22781-22794.
[http://dx.doi.org/10.3390/ijms160922781] [PMID: 26402669]
[18]
Kobayashi, Y.; Saito, K.; Iwasaki, Y.; Ito, R.; Nakazawa, H. Enantiomeric determination of α-lipoic acid in dietary supplements by liquid chromatography/mass spectrometry. Bunseki Kagaku, 2012, 61(2), 109-114.
[http://dx.doi.org/10.2116/bunsekikagaku.61.109]
[19]
Kobayashi, Y.; Ito, R.; Saito, K. Enantiomeric determination of α-lipoic acid in urine by LC/MS/MS. J. Pharm. Biomed. Anal., 2019, 166, 435-439.
[http://dx.doi.org/10.1016/j.jpba.2019.01.042] [PMID: 30731341]
[20]
Chen, X.; Gao, J.; Jiang, Y.; Huang, P.; Xie, Y.; Pi, R.; Zhu, S.; Yao, M. Determination of newly synthesized lipoic acid-niacin dimer in rat plasma by UPLC/electrospray ionization tandem mass spectrometry: assay development, validation and application to a pharmacokinetic study. Biomed. Chromatogr., 2014, 28(2), 213-217.
[http://dx.doi.org/10.1002/bmc.3006] [PMID: 23934776]
[21]
Matsugo, S.; Han, D.; Tritschler, H.J.; Packer, L. Decomposition of alpha-lipoic acid derivatives by photoirradiation-formation of dihydrolipoic acid from alpha-lipoic acid-. Biochem. Mol. Biol. Int., 1996, 38(1), 51-59.
[PMID: 8932519]
[22]
Chng, H.T.; New, L.S.; Neo, A.H.; Goh, C.W.; Browne, E.R.; Chan, E.C.Y. A sensitive LC/MS/MS bioanalysis assay of orally administered lipoic acid in rat blood and brain tissue. J. Pharm. Biomed. Anal., 2010, 51(3), 754-757.
[http://dx.doi.org/10.1016/j.jpba.2009.09.028] [PMID: 19833467]
[23]
Khan, A.; Iqbal, Z.; Watson, D.G.; Khan, A.; Khan, I.; Muhammad, N.; Muhammad, S.; Nasib, H.A.; Iqbal, N. Faiz-Ur-Rehman; Kashif, M. Simultaneous determination of lipoic acid (LA) and dihydrolipoic acid (DHLA) in human plasma using high-performance liquid chromatography coupled with electrochemical detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2011, 879(20), 1725-1731.
[http://dx.doi.org/10.1016/j.jchromb.2011.04.017] [PMID: 21550862]
[24]
Bioanalytical Method Validation. Guidance for Industry, 2018, 83(99)
[25]
Khan, M.I.; Iqbal, Z.; Khan, A. Simultaneous determination of the endogenous free α-lipoic acid and dihydrolipoic acid in human plasma and erythrocytes by RP-HPLC coupled with electrochemical detector. Methods Mol. Biol., 2015, 1208, 345-360.
[http://dx.doi.org/10.1007/978-1-4939-1441-8_25] [PMID: 25323519]
[26]
Sánchez-Guijo, A; González, C; Montero, O; Ramírez, M Determination of lipoic acid, Trolox methyl ether and tocopherols in human plasma by liquid-chromatography and ion-trap tandem mass spectrometry. Biomedical Chromatography: An International Journal Devoted to Research in Chromatographic Methodologies and Their Applications in the Biosciences, 2012, 1228-1233..
[27]
Trivedi, R.K.; Kallem, R.R.; Mamidi, R.N.V.S.; Mullangi, R.; Srinivas, N.R. Determination of lipoic acid in rat plasma by LC-MS/MS with electrospray ionization: assay development, validation and application to a pharamcokinetic study. Biomed. Chromatogr., 2004, 18(9), 681-686.
[http://dx.doi.org/10.1002/bmc.375] [PMID: 15386498]